A review on biomolecular basis of the role of psychological stress in the development and progression of cancer

Over recent years there has been great progress in the scientific knowledge of health and well-being and the body's response to stress and the relationship to the development of cancer. This paper reviews the interrelationship between stress and cancer. The immune system is a specialized network whose activity is highly affected by stress. Stress activates the body's endocrine (hormone) system, which in turn can cause changes in the immune system, the body's defense against infection and disease including cancer. Under stressful conditions the body increases the production of catecholamines via sympathetic nervous system (SNS). Catecholamines suppress certain parts of the immune system and reduce the production of molecules that create inflammation. Catecholamines suppress the cell-mediated immunity (CMI) by reducing macrophages and Th production of type 1 cytokines (e.g. IL-12, TNF-α and IFN-γ), and by stimulating the release of immunosuppressive factors including IL-10 and TGF-α. Hormones associated with SNS activation may favour angiogenic mechanisms in human tumours. In response to chronic stress, catecholamines such as epinephrine and norepinephrine released from the sympathetic nervous system activate b-adrenergic receptors on tumour cells and enhance expression of vascular endothelial growth factor (VEGF), IL-6 and matrix metalloproteinases (MMPs). Stress can also activate the cAMP response element-binding (CREB) protein and create a hypoxic condition. CREB protein and hypoxia regulated genes, e.g. endothelin-1, adrenomedullin, Bcl-2 has been found that are involved in mitogenesis, tumour progression, angiogenesis and apoptosis. Psychosocial stressors and distress have been shown to have direct effects on intracellular processes that are implicated in cancer initiation. Stress may alter cellular DNA repair abilities, may increase the likelihood of retention of damaged DNA, and therefore increase the likelihood of development of malignant cells.